How could a pooled testing policy have performed in managing the early stages of the COVID-19 pandemic? Results from a simulation study (preprint)

A coordinated testing policy is an essential tool for responding to emerging epidemics, as was seen with COVID-19. However, it is very difficult to agree on the best policy when there are multiple conflicting objectives. A key objective is minimising cost, which is why pooled testing (a method that involves pooling samples taken from multiple individuals and analysing this with a single diagnostic test) has been suggested. In this paper, we present results from an extensive and realistic simulation study comparing testing policies based on individually testing subjects with symptoms (a policy resembling the UK strategy at the start of the COVID-19 pandemic), individually testing subjects at random or pools of subjects randomly combined and tested. To compare these testing methods, a dynamic model compromised of a relationship network and an extended SEIR model is used. In contrast to most existing literature, testing capacity is considered as fixed and limited rather than unbounded. This paper then explores the impact of the proportion of symptomatic infections on the expected performance of testing policies. Only for less than 50% of infections being symptomatic does pooled testing outperform symptomatic testing in terms of metrics such as total infections and length of epidemic. Additionally, we present the novel feature for testing of non-compliance and perform a sensitivity analysis for different compliance assumptions. Our results suggest for the pooled testing scheme to be superior to testing symptomatic people individually, only a small proportion of the population (>2%) needs to not comply with the testing procedure.

Resultado funcional en pacientes con infarto cerebral y COVID-19 en Lima, Perú

Resumen Introducción El COVID-19 puede desencadenar un infarto cerebral por varios mecanismos potenciales, entre ellas, la hipercoagulabilidad. Se han reportado peores resultados funcionales en pacientes con infarto cerebral y COVID-19. Objetivo Determinar la asociación entre resultado funcional y COVID-19 en pacientes con infarto cerebral isquémico. Pacientes y métodos Se realizó un estudio de casos y controles comparando a pacientes ingresados a un centro de referencia neurológico en Perú con diagnóstico de infarto cerebral, antes (controles) y después (casos) del inicio de la pandemia por COVID-19. Hubo 31 casos diagnosticados con COVID-19 y 62 controles. Se utilizaron análisis bivariado y análisis de regresión de Poisson de efectos fijos condicionales. Resultados Los casos tenían glucemia basal más alta (133,5, RIQ: 117,5-174 vs 117, RIQ: 101-130, p=0,033) que los controles, recuentos de neutrófilos más altos (7,91, RIQ: 5,93-9,57 vs. 5,96, RIQ: 4,41-7,79, p=0,008), menor recuento de linfocitos (1,48, RIQ: 1,04-1,8 frente a 1,83, RIQ: 1,26-2,32, p=0,025), mayor relación neutrófilos/linfocitos (5,44, RIQ: 4,0-8,1 frente a 3,29, RIQ: 2,25-6,02, p=0,011), mayor NIH scale/score (NIHSS) (14, RIQ: 9-18 vs. 7, RIQ: 5-11, p=0,000) y mayores puntuaciones de Rankin modificadas al alta (4, RIQ: 4-5 vs. 2, RIQ: 1-4) p=0,001). Siete (21,88%) participantes fallecieron en el grupo de casos vs. 1 (1,56%) en los controles (p=0,014). La odds ratio de un mal resultado funcional al alta fue de 1,344 (IC: 1,079-4,039;p=0,029), ajustada por NIHSS al ingreso. Conclusiones Nuestros hallazgos sugieren que los infartos cerebrales asociados a COVID-19 son más graves, tienen un peor resultado funcional y una mayor mortalidad que los infartos cerebrales no relacionados a COVID-19. Introduction COVID-19 seems to induce ischemic stroke by several potential mechanisms including promoting hypercoagulability, and worse functional outcomes have been reported in patients with stroke and the infection with SARS-CoV-2. Objective Determine the association between functional outcome and COVID-19 in patients with stroke. Patients and methods We performed a case control study comparing patients admitted to a neurological reference center in Peru with a diagnosis of stroke before (controls) and after (cases) the onset of the COVID-19 pandemic. There were 31 cases diagnosed with COVID-19 and 62 controls without COVID-19. Bivariate analysis and conditional fixed-effects Poisson regression analysis were used to evaluate the association between the functional outcome of the stroke and COVID-19. Results Cases had higher baseline serum glucose (133.5, IQR: 117.5-174 versus 117, IQR: 101-130, p=0.033) than controls, higher neutrophil counts (7.91, IQR: 5.93-9.57 versus 5.96, IQR: 4.41-7.79, p=0.008), lower lymphocyte counts (1.48, IQR: 1.04-1.8 versus 1.83, IQR: 1.26-2.32, p=0.025), higher neutrophil/lymphocyte ratios (5.44, IQR: 4.0-8.1 versus 3.29, IQR: 2.25-6.02, p=0.011), higher NIH stroke scale/score (NIHSS) (14, IQR: 9-18 versus 7 IQR: 5-11, p=0.000), and higher modified Rankin scores at discharge (4, IQR: 4-5 versus 2, IQR: 1-4), p=0.001). Seven (21.88%) participants died in the group of cases versus 1 (1.56%) in the controls (p=0.014). The odds ratio of having a bad functional outcome at discharge was 1.344 (CI: 1.079-4.039;p=0.029), adjusted by NIHSS at admission. Conclusions Our findings suggest that ischemic strokes associated with COVID-19 are more severe, have worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Lung Ultrasound and High-Resolution Computed Tomography in Suspected COVID-19 Patients Admitted to the Emergency Department: A Comparison

Objective: To analyze the diagnostic accuracy of lung ultrasonography (LUS) and high-resolution computed tomography (HRCT), to detect COVID-19. Materials and Methods: This study recruited all patients admitted to the emergency medicine unit, due to a suspected COVID-19 infection, during the first wave of the COVID-19 pandemic. These patients also who underwent a standardized LUS examination and a chest HRCT. The signs detected by both LUS and HRCT were reported, as well as the sensitivity, specificity, positive predictive value, and negative predictive value for LUS and HRCT. Results: This cohort included 159 patients, 101 (63%) were diagnosed with COVID-19. COVID-19 patients showed more often confluent subpleural consolidations and parenchymal consolidations in lower lung regions of LUS. They also had "ground glass” opacities and "crazy paving” on HRCT, while pleural effusion and pulmonary consolidations were more common in non-COVID-19 patients. LUS had a sensitivity of 0.97 (95% CI 0.92–0.99) and a specificity of 0.24 (95% CI 0.07–0.5) for COVID-19 lung infections. HRCT abnormalities resulted in a 0.98 sensitivity (95% CI 0.92–0.99) and 0.1 specificity (95% CI 0.04–0.23) for COVID-19 lung infections. Conclusion: In this cohort, LUS proved to be a noninvasive, diagnostic tool with high sensitivity for lung abnormalities that were likewise detected by HRCT. Furthermore, LUS, despite its lower specificity, has a high sensitivity for COVID-19, which could prove to be as effective as HRCT in excluding a COVID-19 lung infection.

The Covid-19 pandemic impact on community mental health

The impact of the pandemic is felt by people all over the world. This is caused by stigmatization, discrimination, positive experiences of Covid, and disruption of social support. The purpose of this systematic literature review was to find out the psychological impact during the pandemic on the community. This systematic literature review was compiled by searching for articles from 2020 to 2021 contained in health databases from several journals such as Elsevier, BMC, Index, Cambridge University Press, Dove Press, and Wiley which was performed electronically. The inclusion criteria included in this study were focusing on the impact of the Covid-19 pandemic and mental health. From 20 articles, it was shown that psychological factors also played an important role in adherence to preventive measures in public health (such as vaccination) and how people deal with the threat of this virus infection with good health protocols. A person with a low level of education had a risk of being prone to depression and anxiety. This was because if someone with a high level of education had extensive knowledge about virus transmission so that they were better able to protect and cope with the anxiety and depression. Theoretically, the implication of this study is to enrich insight related to the impact of the Covid-19 pandemic on community mental health. While practically, this study might empower the community to maintain a healthy lifestyle during the pandemic that can prevent mental disorders. We hope this study will also empower stakeholders to create a policy that works in facilitating mental health assistant during the pandemic, especially for the Covid-19 patients in the community. © The Authors, published by EDP Sciences.

Toward a Home Test for COVID-19 Diagnosis: DNA Machine for Amplification-Free SARS-CoV-2 Detection in Clinical Samples.

Nucleic acid-based detection of RNA viruses requires an annealing procedure to obtain RNA/probe or RNA/primer complexes for unwinding stable structures of folded viral RNA. In this study, we designed a protein-enzyme-free nano-construction, named four-armed DNA machine (4DNM), that requires neither an amplification stage nor a high-temperature annealing step for SARS-CoV-2 detection. It uses a binary deoxyribozyme (BiDz) sensor incorporated in a DNA nanostructure equipped with a total of four RNA-binding arms. Additional arms were found to improve the limit of detection at least 10-fold. The sensor distinguished SARS-CoV-2 from other respiratory viruses and correctly identified five positive and six negative clinical samples verified by quantitative polymerase chain reaction (RT-qPCR). The strategy reported here can be used for the detection of long natural RNA and can become a basis for a point-of-care or home diagnostic test.

Quantifying Efficiency Gains of Innovative Designs of Two-Arm Vaccine Trials for COVID-19 Using an Epidemic Simulation Model

Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power of a trial. We illustrate how the operating characteristics of different trial design elements maybe evaluated using a network epidemic and trial simulation model, based on COVID-19 and individually randomized two-arm trials with a binary outcome. We show that “ring” recruitment strategies, prioritizing participants at an imminent risk of infection, can result in substantial improvement in terms of power in the model we present. In addition, we introduce a novel method to make more efficient use of the data from the earliest cases of infection observed in the trial, whose infection may have been too early to be vaccine-preventable. Finally, we compare several methods of response-adaptive randomization (RAR), discussing their advantages and disadvantages in the context of our model and identifying particular adaptation strategies that preserve power and estimation properties, while slightly reducing the number of infections, given an effective vaccine.

Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families.

LAY ABSTRACT: Autistic children who speak few or no words or who have an intellectual disability are the most in need of new understandings and treatments, but the most often left out of the research that can bring these benefits. Researchers perceive difficulties around compliance with instructions, testing, challenging behaviours and family stress. Although research with these children can indeed be difficult, their continuing exclusion is unethical and unacceptable. Drawing on our experiences testing a possible treatment for children with profound autism, we provide 10 practical guidelines related to (1) interacting physically, (2) combining play and testing, (3) responding to challenging behaviour, (4) finding suitable tests, (5) relationships with parents, (6) relationships with siblings, (7) involving stakeholders, (8) planning the testing times, (9) the role of the clinical supervisor and (10) recruiting and retaining participants. We hope that these guidelines will prepare and embolden other research teams to work with profoundly autistic children, ending their historical exclusion from research. These guidelines also could be useful for conducting research with children with intellectual disabilities.

A molecular test based on RT-LAMP for rapid, sensitive and inexpensive colorimetric detection of SARS-CoV-2 in clinical samples.

Until there is an effective implementation of COVID-19 vaccination program, a robust testing strategy, along with prevention measures, will continue to be the most viable way to control disease spread. Such a strategy should rely on disparate diagnostic tests to prevent a slowdown in testing due to lack of materials and reagents imposed by supply chain problems, which happened at the beginning of the pandemic. In this study, we have established a single-tube test based on RT-LAMP that enables the visual detection of less than 100 viral genome copies of SARS-CoV-2 within 30 min. We benchmarked the assay against the gold standard test for COVID-19 diagnosis, RT-PCR, using 177 nasopharyngeal RNA samples. For viral loads above 100 copies, the RT-LAMP assay had a sensitivity of 100% and a specificity of 96.1%. Additionally, we set up a RNA extraction-free RT-LAMP test capable of detecting SARS-CoV-2 directly from saliva samples, albeit with lower sensitivity. The saliva was self-collected and the collection tube remained closed until inactivation, thereby ensuring the protection of the testing personnel. As expected, RNA extraction from saliva samples increased the sensitivity of the test. To lower the costs associated with RNA extraction, we performed this step using an alternative protocol that uses plasmid DNA extraction columns. We also produced the enzymes needed for the assay and established an in-house-made RT-LAMP test independent of specific distribution channels. Finally, we developed a new colorimetric method that allowed the detection of LAMP products by the visualization of an evident color shift, regardless of the reaction pH.

Quantifying Efficiency Gains of Innovative Designs of Two-Arm Vaccine Trials for COVID-19 Using an Epidemic Simulation Model.

Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power of a trial. We illustrate how the operating characteristics of different trial design elements maybe evaluated using a network epidemic and trial simulation model, based on COVID-19 and individually randomized two-arm trials with a binary outcome. We show that "ring" recruitment strategies, prioritizing participants at an imminent risk of infection, can result in substantial improvement in terms of power in the model we present. In addition, we introduce a novel method to make more efficient use of the data from the earliest cases of infection observed in the trial, whose infection may have been too early to be vaccine-preventable. Finally, we compare several methods of response-adaptive randomization (RAR), discussing their advantages and disadvantages in the context of our model and identifying particular adaptation strategies that preserve power and estimation properties, while slightly reducing the number of infections, given an effective vaccine.

Quantifying efficiency gains of innovative designs of two-arm vaccine trials for COVID-19 using an epidemic simulation model (preprint)

Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power of a trial. We illustrate how the operating characteristics of different trial design elements may be evaluated using a network epidemic and trial simulation model, based on COVID-19 and individually randomised two-arm trials with a binary outcome. We show that "ring" recruitment strategies, prioritising participants at high risk of infection, can result in substantial improvement in terms of power, if sufficiently many contacts of observed cases are at high risk. In addition, we introduce a novel method to make more efficient use of the data from the earliest cases of infection observed in the trial, whose infection may have been too early to be vaccine-preventable. Finally, we compare several methods of response-adaptive randomisation, discussing their advantages and disadvantages in this two-arm context and identifying particular adaptation strategies that preserve power and estimation properties, while slightly reducing the number of infections, given an effective vaccine.

A molecular test based on RT-LAMP for rapid, sensitive and inexpensive colorimetric detection of SARS-CoV-2 in clinical samples (preprint)

Until there is an effective implementation of COVID-19 vaccination program, a robust testing strategy, along with prevention measures, will continue to be the most viable way to control disease spread. Such a strategy should rely on disparate diagnostic tests to prevent a slowdown in testing due to lack of materials and reagents imposed by supply chain problems, which happened at the beginning of the pandemic. In this study, we have established a single-tube test based on RT-LAMP that enables the visual detection of less than 100 viral genome copies of SARS-CoV-2 within 30 minutes. We benchmarked the assay against the gold standard test for COVID-19 diagnosis, qRT-PCR, using 177 nasopharyngeal RNA samples. For Ct ≤ 32, the RT-LAMP assay had a sensitivity of 100% and a specificity of 96.1%. Additionally, we set up a RNA extraction-free RT-LAMP test capable of detecting SARS-CoV-2 directly from saliva samples, albeit with lower sensitivity. The saliva was self-collected and the collection tube remained closed until inactivation, thereby ensuring the protection of the testing personnel. As expected, RNA extraction from saliva samples increased the sensitivity of the test. To lower the costs associated with RNA extraction, we performed this step using an alternative protocol that uses plasmid DNA extraction columns. We also produced the enzymes needed for the assay and established an in-house-made RT-LAMP test independent of specific distribution channels. Finally, we developed a new colorimetric method that allowed the detection of LAMP products by the visualization of an evident color shift, regardless of the reaction pH.

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).